Hyaluronan (hyaluronic acid; HA) is a glycosaminoglycan that exists predominantly in connective tissues, skin, cartilage, and in synovial fluid in mammals. Hyaluronan also is the main constituent of the vitreous of the eye. In connective tissue, the water of hydration associated with hyaluronan creates hydrated matrices between tissues. HA is found in the extracellular matrix of many cells, especially in soft connective tissues. HA has a role in various physiological processes, such as in water and plasma protein homeostasis, in the intracellular matrix (Laurent T C et al (1992) FASEB J 6: 2397-2404). Certain diseases are associated with expression and/or production of hyaluronan.
Hyaluronan degrading enzymes, including hyaluronidases, are enzymes that degrade hyaluronan. Various hyaluronan degrading enzymes have been used therapeutically, typically as dispersing and spreading agents in combination with other therapeutic agents. Improved compositions and methods for administration of hyaluronan degrading enzymes for treatment, particularly of hyaluronan-associated diseases and conditions, are needed.